Biomedical subjects
Publications and source records attributed to U Keller.
We demonstrate amplification and compression of 110-nm broad spectra in a spatially dispersed amplifier for what is believed to be the first time and generate 14.8-fs pulses with 450 microJ of energy at a repetition rate of 1 kHz. The amplifier concept is scalable in energy and allows for spectral shaping, which was demonstrated and compared with numerical simulations and showed excellent agreement.
Obesity is a chronic disease resulting from various genetic factors and environmental conditions (nutrition, sedentary life-style, psychological factors). The importance of prevention and therapy of obesity is emerging because of the high prevalence of metabolic complications. The first goal of any therapy must be a stabilisation of weight, followed by a reduction of body weight. Any intervention must be long-acting. Short-acting therapies (diets) result in a regain of body weight in over 90%. The most effective therapy is an integrative concept basing on: change of nutrition by reduction of fat and carbohydrate intake (daily deficit of 500-1000 kcal). psychotherapeutic approach, targeting a long-term change of eating-behaviour and life-style, avoiding guilt feelings. encouraging physical activity. Drugs (Orlistat, Sibutramin) may be helpful in selected cases as a part of a limited treatment, they do not replace changes in lifestyle. Surgical interventions (gastric banding, gastric bypass) can be considered in morbid obesity with the presence of metabolic complications, as they are the most effective way of weight reduction.
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We demonstrate that nonlinear fiber compression is possible at unprecedented average power levels by use of a large-mode-area holey (microstructured) fiber and a passively mode-locked thin disk Yb:YAG laser operating at 1030 nm. We broaden the optical spectrum of the 810-fs pump pulses by nonlinear propagation in the fiber and remove the resultant chirp with a dispersive prism pair to achieve 18 W of average power in 33-fs pulses with a peak power of 12 MW and a repetition rate of 34 MHz. The output beam is nearly diffraction limited and is linearly polarized.
We demonstrate generation of 3.8-fs pulses with energies of up to 15 microJ from a supercontinuum produced in two cascaded hollow fibers. Ultrabroadband dispersion compensation was achieved through a closed-loop combination of a spatial light modulator for adaptive pulse compression and spectral-phase interferometry for direct electric-field reconstruction (SPIDER) measurements as feedback signal.
AIM/HYPOTHESIS: Radiobinding assays (RBA) are unable to differentiate insulin autoantibodies (IAA) from insulin antibodies (IA). We sought to establish whether random peptide phage display might generate reagents with which to distinguish IAA idiotopes from IA idiotopes. METHODS: Two insulin-binding sera were used to select phagotopes from a phage library. The first, designated IAS, came from an insulin-treated patient with the insulin autoimmune syndrome, and was known to contain both IA and a high titre of human insulin specific (B30 threonine dependent) IAA. The second, designated IDD, was taken from a newly-diagnosed IAA(+) Type 1 diabetic patient. Phage colonies selected by insulin-purified IgG extracts of IAS and IDD were selected at random for DNA sequencing, and tested for their reactivity with insulin antibodies and ability to distinguish disease-associated idiotopes. RESULTS: Seven phagotopes bound IAS and the phagotope designated IAS-9, corresponding to sequence KRSRLDV, gave the highest binding standard deviation (SD) score. Seven phagotopes bound IDD and the phagotope designated IDD-10, corresponding to sequence LGRGGSK, bound most strongly. IAS-9 was able to displace insulin binding in IAS and all of ten insulin-treated Type 2 diabetic patients, but not the IAA present in any of the eight patients with newly-diagnosed Type 1 diabetes. IDD-10, on the other hand, could displace insulin binding detected in the sera of eight patients with untreated Type 1 diabetes (IAA), but not in IAS or sera of the insulin-treated Type 2 diabetics. CONCLUSION: Phagotopes provide reagents which between them can distinguish positively as well as negatively diabetes-associated IAA from non-diabetes associated IAA and from IA.
We demonstrate a passively mode-locked diode-pumped thin-disk Yb:YAG laser generating 810-fs pulses at 1030 nm with as much as 60 W of average output power (without using an amplifier). At a pulse repetition rate of 34.3 MHz, the pulse energy is 1.75 microJ and the peak power is as high as 1.9 MW. The beam quality is close to the diffraction limit, with M2 < 1.1.
We describe a method of characterizing ultrashort optical pulses that is based on the technique of spectral phase interferometry for direct electric-field reconstruction and is capable of simultaneously measuring the amplitude and the phase of the electric field of a sub-10-fs pulse at kilohertz acquisition rates on a single-shot basis. Use of this technique results in a dramatic increase (>50x) in acquisition rate compared with that of existing diagnostics for full E-field characterization and opens the door to a range of new experiments in which shot-to-shot phase and amplitude fluctuations are studied at kilohertz rates.
In this paper, we report the first successful demonstration, to our knowledge, of two-photon fluorescence excitation (TPFE) using planar thin-film waveguide structures of macroscopic excitation dimensions (square millimeters to square centimeters in size). The high intensity of excitation light required for TPFE is available not only at a single focus point but along the whole trace of the beam guided in the waveguide structure. Line profiles of the fluorescence excited by TPFE show excellent correlation with the geometry of the launched laser beams. A clear second-order dependence of the fluorescence intensity on the excitation intensity confirms the two-photon character of fluorescence generation. Spectra of the emission generated by one-photon excitation and by two-photon excitation show only minor differences.
Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo-osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.
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We present energy-resolved cross-correlation measurements of an extreme ultraviolet (XUV) pulse, generated as the fifth harmonic (15.5 eV) of an intense 80 fs laser pulse centered at 400 nm. Spectrally resolving the cross-correlation signal allows us to characterize the time-dependent frequency of the XUV pulse. We find that the fifth harmonic has a small negative chirp in excess of that predicted by perturbation theory. In addition, by manipulating the chirp of the driving laser we can induce and measure a positive or a negative chirp on the XUV pulse.
The major risk factor for the development of insulin resistance and type 2 diabetes is obesity. A key role is the new understanding of adipocytes as an endocrine system. Adipocytes secrete numerous substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. There is also a role of free fatty acids by blocking directly intracellular metabolism of glucose and by their lipotoxicity. The pre-receptor metabolism of cortisol may be enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. The new class of thiazolidinediones (glitazones), binding to the peroxisome proliferator activated receptor (PPAR-gamma) lowers the levels of resistin and increases adiponectin, resulting in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance should be an attempt to reduce body weight and to increase physical activity. These are successful means to avoid the development of type 2 diabetes from prediabetic states, as shown recently in 3 independent intervention trials.
Expansion of primitive hematopoietic progenitor cells (HPC) is a major challenge in stem cell biology. Stimulation by growth factors (GF) is essential for proliferation of HPC, while the role of stromal cell coculture for maintenance of progenitor/stem cell potential is unclear. We evaluated the potential of a murine stromal cell layer providing hematopoietic GF to support expansion of human CD34(+) cells. Murine MS-5 cells were transfected with the cDNA encoding huFlt3 ligand and the interleukin6/sinterleukin-6R fusion protein hyper-IL-6. Expansion of CFC and week6 CAFC was at least as efficient in transfected clones compared to control cocultures supported with exogenous GF. Cell numbers reached 17.5- to 62.3- (day 14) and 17.4- to 92.4-fold (day 21) of input cells. Expansion of CFU-GM/Mix was 4.0- to 12.8-fold (day 14) and 4.9- to 11.7-fold (day 21). Primitive week6 CAFC were expanded up to 6.5-fold (day 14) and 6.2-fold (day 21) without exogenous GF. When direct contact of HPC and stromal cells was inhibited, a loss of CFC and much more of CAFC potential was observed with unaffected overall cell proliferation. Here, we show the generation of GF producing murine stromal cells which efficiently support early hematopoiesis without exogenous GF. Direct stromal cell-HPC contact is advantageous for maintenance of differentiation potential.
Chronic stimulation of cardiac beta1-adrenergic receptors contributes to disease progression and mortality in patients and animal models of heart failure. To search for the mechanism of adrenergic impairment of cardiac function in vivo, we studied transgenic mice with cardiac-specific overexpression of beta1-adrenergic receptors. Transgenic mice with cardiac overexpression of beta1-adrenergic receptors showed progressive left ventricular fibrosis starting at 4 months of age. Left ventricular catheterization revealed a modest enhancement of contractility and relaxation at 2 months of age, followed by progressive dysfunction in both parameters and ultimately cardiac failure. When the effects of endogenous catecholamines were blocked by the b-receptor antagonist propranolol, maximal rate of contractility (dp/dtmax) and maximal rate of relaxation (dp/dtmin) were significantly blunted in 2-month-old beta1-receptor transgenic mice. Isolated cardiomyocytes from these animals displayed markedly altered calcium transients with significant prolongation of the intracellular calcium transient compared with nontransgenic littermates. We determined the expression of sarcoplasmic reticulum proteins involved in calcium handling by RNase protection assay and by immunoblotting. Although the expression of calsequestrin, triadin, and phospholamban was not altered, we observed a progressive decrease in junctin abundance in beta1-receptor transgenic mice (Pbeta1-adrenergic receptors.
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The prevalence of obesity is increasing world wide, resulting in morbidity, mortality, and reduced quality of life. The aim of this study was to assess comorbidities and complaints of subjects with morbid obesity in comparison to milder forms of overweight. Therefore, 299 patients visiting our obesity consultation were examined and surveyed prospectively. 41% of the subjects were morbidly obese showing a significantly higher prevalence of arterial hypertension, edema, dyspnea, eczema and depression. Additionally, sleepiness, reduced work capacity, physical inactivity, disadvantages in social life and disturbed eating habits were observed more frequent. Evaluation of subjects with morbid obesity should include a large spectrum of complications, in order to be able to offer a comprehensive support and treatment.
Factor C is an unusual extracellular protein capable of inducing cytodifferentiation in certain Streptomyces strains. The protein is produced by Streptomyces griseus 45H at such a low amount that the study of its mode of action was hindered by the shortage of purified protein. We report here the expression of C-terminally hexa-His-tagged factor C in Streptomyces lividans and Escherichia coli. Expression in S. lividans is low while in E. coli it is relatively high, yielding about 5--10 mg of biologically fully active protein per liter culture.